These studies are designed to evaluate control of the synthesis and degradation of the extracellular matrix particularly as related to collagen. Studies with cultured lung cells demonstrated that both epithelial and mesenchymal cells synthesize collagens Types I and III. These cells do so at a constant rate over extended periods of time. Explants of human lung from patients with idiopathic pulmonary fibrosis disease have shown that these tissues synthesize the same amounts of collagen per cell as do normal tissue, suggesting this disease is one of derangement rather than that of excess collagen. Evaluation of immune and hormonal controls of collagen synthesis suggests that it is possible to regulate the differentiated state of collagen synthesis by external manipulations. Evaluation of collagenases by lung cells have shown that the neutrophil produces a collagenase specific for Type I cells. In addition, cells such as macrophages produce neutral proteases which activate latent collagenases secreted by the same cell. Studies of lung explants have demonstrated that 30 to 40% of newly synthesized collagen is degraded intracellularly. This appears to be independent of other known mechanisms of collagen degradation. Type specific antibodies against collagen Types I and III show that human fetal fibroblasts synthesize both. BIBLIOGRAPHIC REFERENCES: Horwitz, A.L., Hance, A.J., and Crystal, R.G. Granulocyte Collagenase: Selective Digestion of Type I over Type III Collagen. Proc. Nat. Acad. Sci., 1977, 74, 897-901, 1977. Hance, A.J. and Crystal, R.G. Rigid Control of the Synthesis of Collagen Types I and III by Cells in Culture. Nature, 268, 152-154, 1977.